Streptozocin - Zanosar®
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Preparation: Reconstitute ZANOSAR with 9.5 mL of dextrose injection USP, or 0.9% sodium chloride injection USP. The resulting pale-gold solution will contain 100 mg of streptozocin and 22 mg of citric acid per mL. Where more dilute infusion solutions are desirable, further dilution in the above vehicles is recommended. The total storage time for streptozocin after it has been placed in solution should not exceed 12 hours. This product contains no preservatives and is not intended as a multiple-dose vial.
Storage: Unopened vials of ZANOSAR should be stored at refrigeration temperatures (2° to 8°C) and protected from light (preferably stored in carton) Vial: 1000 mg/ 10 ml (100 mg/ml).
Administration: ZANOSAR should be administered intravenously by rapid injection or short 30 - 60 minute infusion or prolonged infusion: 4 to 6 hours. It is not active orally. Although it has been administered intraarterially, this is not recommended pending further evaluation of the possibility that adverse renal effects may be evoked more rapidly by this route of administration.
|Stability / Miscellaneous|
Streptozocin is active in the L1210 leukemic mouse over a fairly wide range of parenteral dosage schedules. In experiments in many animal species, streptozocin induced a diabetes that resembles human hyperglycemic nonketotic diabetes mellitus. This phenomenon, which has been extensively studied, appears to be mediated through a lowering of beta cell nicotinamide adenine dinucleotide (NAD) and consequent histopathologic alteration of pancreatic islet beta cells.
The metabolism and the chemical dissociation of streptozocin that occurs under physiologic conditions has not been extensively studied. When administered intravenously to a variety of experimental animals, streptozocin disappears from the blood very rapidly. In all species tested, it was found to concentrate in the liver and kidney. As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney. Metabolic products have not yet been identified.
INDICATIONS AND USAGE
Use of ZANOSAR in patients with preexisting renal disease requires a judgment by the physician of potential benefit as opposed to the known risk of serious renal damage.
This drug should not be used in combination with or concomitantly with other potential nephrotoxins.
When exposed dermally, some rats developed benign tumors at the site of application of streptozocin. Consequently, streptozocin may pose a carcinogenic hazard following topical exposure if not properly handled. (See DOSAGE AND ADMINISTRATION.)
DOSAGE AND ADMINISTRATION
Two different dosage schedules have been employed successfully with ZANOSAR.
Daily Schedule—The recommended dose for daily intravenous administration is 500 mg/m2 of body surface area for five consecutive days every six weeks until maximum benefit or until treatment-limiting toxicity is observed. Dose escalation on this schedule is not recommended.
Weekly Schedule—The recommended initial dose for weekly intravenous administration is 1000 mg/m2 of body surface area at weekly intervals for the first two courses (weeks). In subsequent courses, drug doses may be escalated in patients who have not achieved a therapeutic response and who have not experienced significant toxicity with the previous course of treatment. However, A SINGLE DOSE OF 1500 mg/m2 BODY SURFACE AREA SHOULD NOT BE EXCEEDED as a greater dose may cause azotemia. When administered on this schedule, the median time to onset of response is about 17 days and the median time to maximum response is about 35 days. The median total dose to onset of response is about 2000 mg/m2 body surface area and the median total dose to maximum response is about 4000 mg/m2 body surface area.
The ideal duration of maintenance therapy with ZANOSAR has not yet been clearly established for either of the above schedules.
For patients with functional tumors, serial monitoring of fasting insulin levels allows a determination of biochemical response to therapy. For patients with either functional or nonfunctional tumors, response to therapy can be determined by measurable reductions of tumor size (reduction of organomegaly, masses, or lymph nodes).
Caution in the handling and preparation of the powder and solution should be exercised, and the use of gloves is recommended. If the sterile powder of ZANOSAR or a solution prepared from ZANOSAR contacts the skin or mucosae, immediately wash the affected area with soap and water.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
| 1) [PACKAGE INSERT DATA] : Zanosar (Streptozocin) powder, for solution. [Sicor Pharmaceuticals, Inc.] Revised: 03/2006.
2) Solimando, Dominic A. Drug Information Handbook for Oncology: A Complete Guide to Combination Chemotherapy Regimens, 8th ed. Hudson, OH: Lexi-Comp, Inc.; 2010.